Atherosclerosis is a disease wherein fatty substances (lipids), hereinafter referred to as atheromatous plaques, form deposits in and beneath the intima which is the innermost tissue lining arteries and veins. Clinical symptoms occur because the mass of the atherosclerotic plaque reduces blood flow through the involved artery, comprising tissue or organ function.
In the co-pending patent application Ser. No. 443,958 now U.S. Pat. No. 4,512,762, a treatment for artherosclerosis is disclosed. This treatment is based on the discovery that hematoporphyrin derivative (HPD) selectively accumulates in atheromatous plaques and not in the adjacent normal tissue. These plaques can be treated or removed by photoactivating the porphyrin(s) with visible light, which apparently causes the release of singlet oxygen which in turn damages the atheromatous plaque cell. This cytotoxic mechanism is discussed in "Identification of Singlet Oxygen As The Cytotoxic Agent in Photoinactivation of A Murine Tumor." by K. R. Weishaupt, C. J. Gromer, and T. J. Dougherty, Cancer Research, 36:2326-2329 (1976).
Photoactivation of the HPD, as taught by patent application Ser. No. 443,958 now U.S. Pat. No. 4,512,762, can be accomplished by either of two different techniques. With one technique, the patient is catheterized with a light-emitting catheter inserted into the diseased artery until the light-emitting portion of the catheter is adjacent the atheromatous plaque. With the alternative technique, light-emitting liquid, such as the aqueous peroxyalate chemiluminescent system made by American Cyanamid Co., is injected into the vascular tree so that the liquid, which mixes freely with the blood or a blood replacement, perfuses the diseased artery and photoactivates the absorbed hematoporphyrin.
The referenced application teaches an invasive means for reducing or removing atheromatous plaques. No conventional invasive test is currently available which can be used to reliably image or quantitate atheromatous plaques. Arteriography is a definitive procedure for determining the extent of human encroachment by plaques, but cannot be used to image the plaques per se. During a catherization procedure, an ultrathin fiberoptic catheter (an angioscope) is introduced into the arterial tree. The lumen may be visualized directly by displacing the blood with an optically clear medium such as one of the presently available perfluorocarbon-containing blood replacements which provide both oxygen transport and maintain oncotic pressure. Demarcation between the artheromatous plaque and the normal artery wall is ambiguous, however, because the luminal surface of both tissues is the same whitish color. A technique for direct visualization of the blood vessel walls is disclosed in "In Vivo Coronary Angioscopy" by J. Richard Spears, H. John Marais, Juan Serur, Oleg Pomerantzeff, Robert P. Geyer, Robert S. Sipzener, Ronald Weintraub, Robert Thurer, Sven Paulin, Richard Gerstin and William Grossman, J. Amer. College of Cardiology, 1(5):1311-1314(1983).
Noninvasive techniques for detecting or defining atheromatous plaques are also quite limited. Ultrasound can be used to detect lumen encroachment by atheromatous plaques in the carotid artery, fluoroscopy can be used to identify plaques if they contain calcium deposits, and NMR can occasionally be used to identify plaques. None of these is a very reliable means for the noninvasive imaging of atheromatous plaques. As a result, currently used non-invasive tests for atherosclerotic coronary artery disease are based solely on the physiological consequences of lumen encroachment by the atheromatous plaques. Such tests include ECG, ECG stress testing, thallium perfusion imaging, and radionuclide ventriculography. A severe stenosis (approximately 70% diameter reduction) must be present, however, before an abnormality is detected by these tests.
The primary reason that atheromatous plaques cannot be reliably detected by the use of currently available noninvasive techniques is that atheromatous plaques do not differ significantly from surrounding tissues in any of the physio-chemical properties which alter the signals detected by the techniques.
It is therefore an objective of the present invention to provide a means for detecting, imaging, or quantifying atheromatous plaques which can be used with both invasive and noninvasive techniques.